Immunotherapeutic Formulations with Interleukin-2-Neutralizing Capacity

Abstract

The present invention is related to pharmaceutical compositions based on vaccines and monoclonal antibodies that neutralize the Interleukin-2, which are useful in the treatment of tumors. Particularly the present invention is related to therapeutic formulations able to increase the immunogenicity of the IL-2 conjugated to the carrier protein P64k from the neisseria meningitidis in montanide ISA 51 adjuvant for the induction of IL-2 neutralizing autoantibodies and the effective methods for the treatment of tumors, including breast cancer and melanoma. Furthermore, the present invention is related to therapeutic combination of the IL-2 based vaccine with other cancer vaccines based on specific tumor antigens or tumor growth factors, as well as chemotherapeutics agents or radiotherapy of standard use for cancer treatment.

1 . A therapeutic formulation to elicit an immune response against IL-2, useful for the treatment of cancer patients, comprising at least one of:
 A.—IL-2 or any derivate thereof coupled to any carrier protein by genetically or chemical conjugation that contains an appropriate adjuvant;   B.—a monoclonal antibody anti-IL-2;   C.—a cancer vaccine based on specific tumor antigens or growth factors;   D.—a monoclonal antibody anti-CD25.   
     
     
         2 . The administration of a therapeutic formulation to elicit an immune response against IL-2, according to  claim 1 , comprising administering simultaneously or sequentially at least one selected from A+C, A+D, B+C, B+D. 
     
     
         3 . A therapeutic formulation to elicit an immune response against IL-2, according to  claim 1 , comprising IL-2 or a derivate thereof coupled to a carrier protein, and an appropriate adjuvant. 
     
     
         4 . A therapeutic formulation to elicit an immune response against IL-2 according to  claim 1 , comprising IL-2 coupled to a carrier protein, and an appropriate adjuvant. 
     
     
         5 . A therapeutic formulation to elicit an immune response against IL-2 according to  claim 4 , wherein the carrier protein comprises P64k derived from  neisseria meningitidis.    
     
     
         6 . A therapeutic formulation to elicit an immune response against IL-2, according to  claim 5 , wherein the adjuvant is selected from the group consisting of aluminium hydroxide and montanide ISA 51. 
     
     
         7 . A therapeutic formulation to elicit an immune response against IL-2 according to  claim 6 , wherein the adjuvant is montanide ISA 51. 
     
     
         8 . A therapeutic formulation to elicit an immune response against IL-2 according to  claim 1 , comprising a chemical conjugated between IL-2 and P64k. 
     
     
         9 . A therapeutic formulation to elicit an immune response against IL-2 according to  claim 1 , comprising a fusion protein between IL-2 and P64k. 
     
     
         10 . A therapeutic formulation to elicit an immune response against IL-2 according to  claim 1 , comprising a fusion protein between peptides derived from IL-2 and P64k. 
     
     
         11 . A therapeutic formulation to elicit an immune response against IL-2 according to  claim 1 , comprising a specific monoclonal antibody against human IL-2. 
     
     
         12 . A method for administering the therapeutic formulation of  claim 1  to elicit an immune response against IL-2 comprising administering IL-2 or a derivative thereof coupled to a carrier protein and an adjuvant in combination with a cancer vaccine based on specific tumor antigens or growth factors. 
     
     
         13 . The method for administering the therapeutic formulation of  claim 1  to elicit an immune response against IL-2 wherein the cancer vaccine comprises EGF. 
     
     
         14 . The method for administering the therapeutic formulation of  claim 12  to elicit an immune response against IL-2 comprising administering IL-2 or a derivative thereof coupled to a carrier protein and an adjuvant in combination with a specific monoclonal antibody anti-CD25. 
     
     
         15 . The method of administering the therapeutic formulation of  claim 13  for eliciting an immune response against IL-2 further comprising a specific monoclonal antibody anti-CD25. 
     
     
         16 . A therapeutic formulation according to  claim 1 , comprising, a medicament, said medicament elicits an immune response against IL-2 so as to inhibit the growth of tumours in cancer patients. 
     
     
         17 . The use of the therapeutic formulation of  1 , comprising inhibiting the growth of tumours. 
     
     
         18 . A therapeutic formulation to elicit an immune response against IL-2, said formulation comprising:
 (a) at least one selected from an IL-2 carrier protein conjugate and a monoclonal antibody anti-IL-2; and   (b) at least one selected from a carrier vaccine and a monoclonal antibody anti-CD25.   
     
     
         19 . The therapeutic formulation of  claim 18 , further comprising an adjuvant. 
     
     
         20 . The therapeutic formulation of  claim 18 , wherein the carrier protein comprises P64k derived  neisseria meningitidis.